Two cases of late-diagnosed ovotesticular disorder of sex development.

Ovotesticular disorder of sex development (ovotesticular DSD) is defined as the presence of testicular and ovarian tissue in the same individual. Both external and internal genitalia of patients with ovotesticular DSD display a spectrum of phenotypes. Most children present with ambiguous genitalia in combination with unilateral or bilateral undescended gonads. We experienced two late-diagnosed children who presented with proximal hypospadias and bilateral scrotal gonads. One should consider the possibility of ovotesticular DSD when managing patients with proximal hypospadias even if both gonads are palpable in the scrotum.


INTRODUCTION
Ovotesticular disorder of sex development is defined as the presence of both testicular and ovarian tissues in the same individual, which may take the form of one ovary and one testis or, more commonly, one or two ovotestes. Most children present with ambiguous genitalia in combination with unilateral or bilateral undescended gonads. [1,2] Herein we present our experience of two late-diagnosed children with ovotesticular DSD.

Case 1
A 5-year-old boy was referred with hypospadias cripple. At four years of age, he underwent onestage repair using the onlay island flap technique for penoscrotal hypospadias at another hospital. Repair was unsuccessful. The meatus was located at the penoscrotal junction at the first visit to our hospital. Although the ventral curvature persisted, no visible scar was noted in the urethral plate. Both gonads were palpated in the scrotum. The gonads were considered as testes on palpation.
Orthoplasty for the persistent ventral curvature and tubularized incised plate urethroplasty for meatal advancement was performed. Although the ventral curvature improved, glans dehiscence occurred. It resulted in a subcoronal meatus. Plan for a twostage repair using a buccal mucosal graft was declined by the family. During the follow-up, nodules suspicious for ovarian tissues were palpated in the upper pole of both testes. Karyotype analysis revealed 46,XX without SRY gene. The levels of follicle stimulating hormone, luteinizing hormone, testosterone and estradiol were 10.18 mIU/ml, 4.03 mIU/ml, 341 ng/dl and less than 10 pg/ml, respectively. Subsequently, he underwent cystoscopy, laparoscopy, and scrotal exploration for evaluation of DSD.
Cystoscopy showed a 6.5-cm vagina connecting to the posterior urethra. Laparoscopy demonstrated that each vas deferens ran toward its respective side of the internal inguinal ring. Neither uterus nor fallopian tubes were noted. Scrotal exploration revealed a firm nodule resembling an ovary in the upper pole of each testis (Fig. 1). The nodules were removed and testicular biopsies were performed. The remaining testes were placed in the scrotum. Histological analysis revealed the removed nodules were normal ovarian tissues, with the margin containing the testicular tissue. The biopsied specimen was immature testicular tissue containing seminiferous tubules and Leydig cells. Testicular atrophy was not recognized 48 months after the surgery. As a result, karyotype and histological analysis confirmed that he had ovotesticular DSD eight years after the first visit. He has developed normal pubertal maturation.

Case 2
A two-month-old boy was referred with proximal shaft hypospadias. On physical examination, penoscrotal transposition was noted in addition to the small phallus. Both gonads were palpated in the scrotum. The gonads were considered as testes on palpation. At two years of age, he underwent onestage repair using a preputial skin graft without preoperative hormonal stimulation. Glans dehiscence occurred after the surgery, resulting in a subcoronal meatus. At three year of age, he underwent scrotoplasty using a modified Glenn-Anderson technique for penoscrotal transposition. During the follow-up, nodules suspicious for ovarian tissues were palpated in the upper pole of both testes. Karyotype analysis revealed 46,XX without SRY gene. The levels of follicle stimulating hormone, luteinizing hormone, testosterone and estradiol were 0.42 mIU/ml, less than 0.07 mIU/ml, less than 0.05 ng/dl and less than 10 pg/ml, respectively. Subsequently, he underwent cystoscopy, laparoscopy, and scrotal exploration for evaluation of DSD.
Cystoscopy showed a normal urethra without a vagina. Laparoscopy did not clearly demonstrate both vasa deferens. Neither uterus nor fallopian tubes were noted. Scrotal exploration revealed a firm nodule resembling an ovary in the upper pole of each testis (Fig. 2). The nodules were removed and the remaining testes were placed in the scrotum. Histological analysis revealed the removed nodules were normal ovarian tissues, with the margin containing the immature testicular tissue (few germ cells, no Leydig cells). Testicular atrophy was not recognized 19 months after the surgery. As a result, karyotype and histological analysis confirmed that he had ovotesticular DSD. At 10 year of age, the levels of follicle stimulating hormone, luteinizing hormone, testosterone and estradiol were 1.32 mIU/ml, less than 0.07 mIU/ml, less than 0.03 ng/dl and less than 10 pg/ml, respectively. He has not developed pubertal maturation yet.

DISCUSSION
In ovotesticular DSD the ovotestis is the most common gonad, and it may reside at any point along the path of testicular descent. [ One should consider the possibility of ovotesticular DSD when managing patients with proximal hypospadias even if both gonads are palpated in the scrotum. In such cases, careful palpation should be performed to rule out asymmetric polar anatomy of the gonads although routine karyotyping is unnecessary.